PMID- 12413399
OWN - NLM
STAT- MEDLINE
DCOM- 20030314
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 370
IP  - Pt 1
DP  - 2003 Feb 15
TI  - Hypoxic activation of the atrial natriuretic peptide gene promoter through direct 
      and indirect actions of hypoxia-inducible factor-1.
PG  - 149-57
AB  - Atrial natriuretic peptide (ANP) is a cardiac peptide, the transcription of which 
      is up-regulated in the ischaemic ventricle. However, the molecular mechanism of 
      ANP induction is unclear. This study demonstrated that ANP mRNA expression in rat 
      ventricular myocardium is induced in an early phase of ischaemia, preceded by 
      hypoxia-inducible factor-1 (HIF-1) alpha expression. The ANP gene was also 
      induced by hypoxia or HIF-1 inducers such as CoCl2 and desferrioxamine in H9c2 
      and neonatal cardiomyocytes. The 2307 bp 5'-flanking region of the rat ANP gene 
      was cloned and fused to the luciferase gene. Evidence of the promoter activity 
      was only apparent in the myocytes and was induced by hypoxia and HIF-1 inducers. 
      The overexpression of HIF-1alpha markedly enhanced ANP promoter activity, and a 
      dominant-negative isoform completely suppressed it. We demonstrated that the 
      promoter regions are essential for hypoxic ANP induction. One promoter region, 
      containing the HIF-1-binding sequence, is regulated directly by HIF-1. The other 
      region is also activated by HIF-1 despite having no HIF-1-binding sequence. These 
      results suggest that HIF-1 enhances the transactivation of the ANP gene in 
      hypoxic myocytes, implying that stimulation of the ANP promoter by HIF-1 may in 
      fact be responsible for the induction of the ANP gene in ischaemic ventricular 
      myocardium.
FAU - Chun, Yang-Sook
AU  - Chun YS
AD  - Human Genome Research Institute and Cancer Research Institute, BK21 Human Life 
      Sciences, Seoul National University College of Medicine, 28 Yongon-dong, 
      Chongno-gu, Seoul 110-799, South Korea.
FAU - Hyun, Ju-Yeon
AU  - Hyun JY
FAU - Kwak, Yong-Geun
AU  - Kwak YG
FAU - Kim, In-San
AU  - Kim IS
FAU - Kim, Chan-Hyung
AU  - Kim CH
FAU - Choi, Eunjoo
AU  - Choi E
FAU - Kim, Myung-Suk
AU  - Kim MS
FAU - Park, Jong-Wan
AU  - Park JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
SB  - IM
MH  - Animals
MH  - Atrial Natriuretic Factor/*genetics
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - DNA Primers
MH  - DNA-Binding Proteins/*physiology
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression Regulation/*physiology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Immunohistochemistry
MH  - Myocardial Ischemia/metabolism
MH  - Myocardium/metabolism
MH  - Nuclear Proteins/*physiology
MH  - *Promoter Regions, Genetic
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Transcription Factors
MH  - United States
PMC - PMC1223144
EDAT- 2002/11/05 04:00
MHDA- 2003/03/15 04:00
PMCR- 2003/08/15
CRDT- 2002/11/05 04:00
PHST- 2002/11/04 00:00 [accepted]
PHST- 2002/10/30 00:00 [revised]
PHST- 2002/07/10 00:00 [received]
PHST- 2002/11/05 04:00 [pubmed]
PHST- 2003/03/15 04:00 [medline]
PHST- 2002/11/05 04:00 [entrez]
PHST- 2003/08/15 00:00 [pmc-release]
AID - BJ20021087 [pii]
AID - 10.1042/BJ20021087 [doi]
PST - ppublish
SO  - Biochem J. 2003 Feb 15;370(Pt 1):149-57. doi: 10.1042/BJ20021087.